Treatment of headache

ABSTRACT

Headache treatment methods are described and include providing, an energy delivery device; locating a secondary or higher-order branch of a postganglionic nerve that provides innervation for a patient&#39;s head, by identifying a target region of the patient&#39;s head that includes the nerve branch; positioning, within the target region, a portion of the energy delivery device; and applying, from the positioned portion of the energy delivery device to the target region, an amount of energy effective to result in a stimulation activity of the nerve branch; and, after observing the stimulated nerve branch activity, delivering, from the energy delivery device to the nerve branch, energy in an amount effective to reduce a headache severity in the patient.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/599,161 filed Jan. 16, 2015 (now U.S. Pat. No. 9381,065 issued July5, 2016), which is a continuation of U.S. patent application Ser. No.14/156,033 filed Jan. 15, 2014 (now U.S. Pat. No. 8,938,302 issued Jan.20, 2015), which is a continuation of U.S. patent application Ser. No.12/605,295 filed Oct. 23, 2009 (now U.S. Pat. No. 8,666,498 issued March4, 2014), which claims the benefit of U.S. Provisional Application No.61/108,820, filed on Oct. 27, 2008, the content of which is incorporatedherein by reference in its entirety.

BACKGROUND OF THE INVENTION

1 . Field

Embodiments disclosed herein relate to treatment of headache.

2 . Description of the Related Art

Headache pain is highly prevalent amongst people worldwide. The WorldHealth Organization estimates that one person in 20 has a headacheeveryday or almost every day. In addition, approximately 70% of adultsin developed countries are afflicted with tension or “stress” headaches.The World Health Organization estimates that 240 million peopleworldwide each year are afflicted with migraine headaches. Headache paincan impose disabling hardships on afflicted individuals such as personalsuffering, impaired quality of life, and impaired financial status.Headache pain, in some instances together with the constant fear of suchpain, can damage an afflicted individuals family life, social life,workplace productivity, etc. Moreover, individuals who suffer long-termchronic headache pain can be predisposed to suffer other illnesses; forexample, depression is three times more common in people afflicted withrecurring migraine or severe headaches than in people who do not sufferfrom recurring migraine or severe headaches.

BRIEF SUMMARY OF THE INVENTION

In certain embodiments, a headache treatment method is provided. Themethod includes providing an energy delivery device; locating asecondary or higher-order branch of a postganglionic nerve that providesinnervation for a patient's head, wherein the locating comprises:identifying a target region, of the patient's head, comprising the nervebranch; positioning, within the target region, a portion of the energydelivery device, and applying, from the positioned portion of the energydelivery device to the target region, an amount of energy effective toresult in a stimulation activity of the nerve branch; and afterobserving the stimulated nerve branch activity, delivering, from theenergy delivery device to the nerve branch, energy in an amounteffective to reduce a headache severity in the patient.

In certain embodiments of the method, the headache severity comprises atleast one of a degree of pain, a frequency, and a duration of theheadache. In certain embodiments of the method, the nerve branchcomprises a motor neuron. In certain embodiments of the method, thenerve comprises a sympathetic neuron. Certain embodiments of the methodinvolve detecting the stimulated nerve branch activity withelectromyography. Certain embodiments of the method involve detectingthe stimulated nerve branch activity as nerve conduction between twoelectrodes. In certain embodiments of the method, the nerve branchcomprises a tertiary or higher-order branch. Certain embodiments of themethod also involve locating a sensory nerve provides innervation forthe patient's head; and applying, from the positioned portion of theenergy delivery device to the sensory nerve, an amount of energyeffective to reduce the headache severity in the patient.

In certain embodiments of the method, the delivered energy compriseselectromagnetic energy. In certain embodiments of the method, thedelivered energy comprises at least one of ultrasound energy, heatenergy, and cryogenic energy. In certain embodiments of the method, thedelivered energy comprises at least one of an ultraviolet light energy,a blue light energy, an infrared light energy, an x-ray energy, agamma-ray energy, and a microwave energy. In certain embodiments of themethod, the amount of delivered energy effective to reduce the headachepain is effective to ablate the neuron.

In certain embodiments of the method, the motor neuron innervates amuscle selected from the group consisting of a frontalis muscle, acorrugator superculii muscle, an orbicularis oculi muscle, a procerusmuscle, a nasalis muscle, a levator labii superioris muscle, azygomaticus major muscle, a zygomaticus minor muscle, a levator anguiioris muscle, a modialus muscle, a platysma paris muscle, a platysmalabialis muscle, a depressor labii inferioris muscle, a depressor angulioris muscle, a platysma pars modialaris muscle, a platysma pars labialismuscle, a platysma pars mandibularis muscle, a temporalis muscle, anoccipatalis muscle, a risorius muscle, a masseter muscle, a spleniuscapitus muscle, a stylohyoid muscle, a suboccipital muscle, a digastricmuscle, a buccinator muscle, a sternocleidomastoid muscle, a levatorscapulae muscle, a scalenus medius muscle, a scalenus anterior muscle, atrapezius muscle, and an omohyoid muscle.

In certain embodiments of the method, the nerve is selected from atleast one of a facial nerve, an abducens nerve, an oculomotor nerve, atrochlear nerve, a trigeminal nerve, a glossopharangeal nerve, ahypoglossal nerve, and an accessory nerve. In certain embodiments of themethod, the nerve branch is a branch of a facial nerve selected from atemporal branch, a zygomatic branch, a buccal branch, a mandibularbranch, and a cervical branch. In certain embodiments of the method, thenerve branch is selected from at least one of a superior division of theoculomotor nerve and an inferior division of the oculomotor nerve. Incertain embodiments of the method, the nerve branch is a mandibularbranch of the trigeminal nerve. In certain embodiments of the method,the nerve branch is a mylohyoid branch of the mandibular branch. Incertain embodiments of the method, the nerve branch is a pharyngealbranch of the glossopharyngeal nerve. In certain embodiments of themethod, the nerve branch is a branch of the hypoglossal nerve selectedfrom a meningeal branch, a thyrohyoid branch, a descending branch, and amuscular branch in certain embodiments of the method, the nerve branchis an angular nerve. In certain embodiments of the method, the sensorynerve comprises at least one of a second occipital nerve, a thirdoccipital nerve, a zygomaticotemporal nerve, a trigeminal nerve, aglossopharyngeal nerve.

In certain embodiments, another method, of treating headache, isprovided. The other method includes providing an energy delivery device:locating a secondary or higher-order branch of a postganglionic nervethat provides innervation for a patient's head, wherein the locatingcomprises: identifying a target region, of the patient's head,comprising the nerve branch: positioning, within the target region, aportion of the energy delivery device: and applying, from the positionedportion of the energy delivery device to the target region, an amount ofenergy effective to result in a stimulation activity of the nervebranch; alter observing the stimulated nerve branch activity;delivering, from the energy delivery device to the nerve branch, energyin an amount effective to reduce a headache severity in the patient; andadministering, to a target area of the patient's head comprising a motorneuron, a neurotoxin; wherein, in combination, the amount of deliveredenergy and the amount of administered neurotoxin are effective to reducea headache severity in the patient.

In certain embodiments of the other method, the headache severitycomprises at least one of a degree of pain, a frequency, and a durationof the headache. In certain embodiments of the other method, the nervebranch comprises a motor neuron, a sympathetic neuron, or a tertiary orhigher-order branch. In certain embodiments of the other method, themethod further includes at least one of detecting the stimulated nervebranch activity with electromyography, and detecting the stimulatednerve branch activity as nerve conduction between two electrodes.

In certain embodiments of the other method, the method further includeslocating a sensory nerve innervating the patient's head, and applying,from the positioned portion of the energy delivery device to the sensorynerve, an amount of energy effective to reduce the headache severity inthe patient. In certain embodiments of the other method, the sensorynerve comprises at least one of a second occipital nerve, a thirdoccipital nerve, a zygomaticotemporal nerve, a trigeminal nerve, aglossopharyngeal nerve.

In certain embodiments of the other method, the delivered energycomprises at least one of ultrasound energy, heat energy, cryogenicenergy, electromagnetic energy, ultraviolet light energy, a blue lightenergy, an infrared light energy, an x-ray energy, a gamma-ray energy,and a microwave energy. In certain embodiments of the other method, theamount of delivered energy effective to reduce the headache pain iseffective to ablate the neuron.

In certain embodiments of the other method, the motor neuron innervatesa muscle selected from the group consisting of a frontalis muscle, acorrugator superculii muscle, an orbicularis oculi muscle, a procerusmuscle, a nasalis muscle, a levator labii superioris muscle, azygomaticus major muscle, a zygomaticus minor muscle, a levator anguiioris muscle, a modialus muscle, a platysma paris muscle, a platysmalabialis muscle, a depressor labii inferioris muscle, a depressor angulioris muscle, a platysma pars modialaris muscle, a platysma pars labialismuscle, a platysma pars mandibularis muscle, a temporalis muscle, anoccipatalis muscle, a risorius muscle, a masseter muscle, a spleniuscapitus muscle, a stylohyoid muscle, a suboccipital muscle, a digastricmuscle, a buccinator muscle, a sternocleidomastoid muscle, a levatorscapulae muscle, a scalenus medius muscle, a scalenus anterior muscle, atrapezius muscle, and an omohyoid muscle.

In certain embodiments of the other method, the nerve is selected fromat least one of a facial nerve, an abducens nerve, an oculomotor nerve,a trochlear nerve, a trigeminal nerve, a glossopharangeal nerve, ahypoglossal nerve, and an accessory nerve. In certain embodiments of theother method, the nerve branch comprises a branch of a facial nerveselected from a temporal branch, a zygomatic branch, a buccal branch, amandibular branch, and a cervical branch. In certain embodiments of theother method, the nerve branch is selected from at least one of asuperior division of the oculomotor nerve and an inferior division ofthe oculomotor nerve.

In certain embodiments of the other method, the nerve branch comprises amandibular branch of the trigeminal nerve, a mylohyoid branch of themandibular branch, or a pharyngeal branch of the glossopharyngeal nerve.In certain embodiments of the other method, the nerve branch comprises abranch of the hypoglossal nerve selected from a meningeal branch, athyrohyoid branch, a descending branch, and a muscular branch. Incertain embodiments of the other method, the nerve branch comprises anangular nerve.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide furtherunderstanding and are incorporated in and constitute a part of thisspecification, illustrate disclosed embodiments and together with thedescription serve to explain the principles of the disclosedembodiments. In the drawings:

FIG. 1 is a stylized illustration of certain muscles of a human head.

FIG. 2 is a stylized illustration of certain nerves of a human head.

FIG. 3 is a stylized illustration of certain nerves of a human head.

DETAILED DESCRIPTION OF THE INVENTION

The international headache society has classified headache disorders andfacial pain into many groups. The groups include: migraine headache;tension headache; cluster headache; miscellaneous headache unassociatedwith structural lesions; headache associated with head trauma; andheadache associated with vascular disorders. The groups also includeheadache associated with non-vascular intracranial disorder; headacheassociated with substances or their withdrawal; headache associated withnon-cephalic infections; headache associated with metabolic disorders;headache associated with disorders of facial or cranial structures;headache associated with cranial neuralgias; and non-classifiableheadache.

Vascular headaches include a variety of conditions resulting from headpain generating events at interfaces between blood vessels and nervefibers. For instance, afferent nociceptive nerve fibers enervatingmeningeal blood vessels can become activated in response to inflammatoryand related events, resulting in pain. A common vascular headache ismigraine headache, which can last 72 hours or more. Migraine headachecharacteristics include unilateral or bilateral head pain of moderate tosevere intensity which can be associated with nausea, vomiting,sensitivity to light, sensitivity to sound, and visual disturbances. Thetrigeminal-vascular system is believed to play a role in the genesis ofmany migraine headaches.

Vascular headaches also include “cluster” headache, which are commonlycharacterized by frequent, transient, attacks of a high-intensity,unilateral head pain. Cluster headache pain is often described as aburning, stabbing, or piercing sensation localized behind the eye or inthe region, and can manifest pain in the face, temple, nose, cheek,and/or upper gum on the affected side. Cluster headaches can beaccompanied by autonomic symptoms lacrimation and nasal congestion), canoccur several times in a single day over the course of several weeks ormonths, and can return after disappearing for several weeks, months, oryears. Although uncertain, the trigeminal-autonomic system appears toplay a role in the genesis of cluster headache. Cluster headache is aneurological disease that involves, as its most prominent feature, animmense degree of pain. “cluster” refers to the tendency of theseheadaches to occur periodically, with active periods interrupted byspontaneous remissions.

Tension headaches (or “tension-type headaches”) are frequentlycharacterized by bilateral head pain of mild to moderate intensity, andtension headaches can be chronic. Tension headache pain is oftendescribed as a pressing, dull, aching, and/or pulsating pain. Thegenesis of many tension headaches appears to involve the myo-facialsystem, and tension headaches can be caused by, for example, thetightening of facial and neck muscles, teeth clinching, teeth grinding,and poor posture. Tension headaches are the most common type of primaryheadaches. The pain can radiate from the neck, back, eyes, or othermuscle groups in the body.

Trigeminal neuralgia comprises an affliction of the trigeminal nerve,and results in severe head pain. Trigeminal neuralgia pain is oftendescribed as quick bursts of lightning-bolt, machine-gun, orelectric-shock type of pain which usually affects one side of the heador face in short bursts lasting a few seconds and repeated many timesover the course of an attack. Occipital neuralgia comprises anaffliction of the occipital nerves, and results in severe head pain,which frequently originates in the neck and spreads up the forehead andscalp. Occipital neuralgia can be caused by physical stress, trauma toor compression of the greater or lesser occipital nerves, tumorsinvolving the second and third cervical dorsal root, or repeatedcontractions of neck muscles.

Cervicogenic headaches are frequently characterized by pain signals fromnerves originating in neck structures, such as the joints, ligaments,muscles, and cervical discs, which synapse in the same brainstem nucleias nerve fibers of the trigeminal nerve. Since the trigeminal nerve isresponsible for the perception of head pain, the patient experiences thesymptoms of headache pain. Many cervicogenic headaches are characterizedby pain similar to tension headache pain, but some cervicogenicheadaches are characterized by pain similar to migraine or clusterheadache pain.

Several approaches for treating head pain associated with a wide varietyof headaches have been developed, and can involve preventativetreatment, treatment to relieve specific symptoms, and/or abortivetreatment. For instance, serotonin receptor agonists, given early at theonset of pain associated with migraine headache, can be effective in upto 70% of patients. But serotonin receptor agonists are frequently onlypartially effective at attenuating migraine headaches, and rebound painfrequently occurs as drug levels fall. Moreover, serotonin agonistsfrequently become ineffective over repeated usages, and side effects ofserotonin receptor agonists include dizziness, shortness of breath, andchest pain. Other drugs used to prevent migraines include beta-blockers,calcium channel blockers, nsaids, antidepressants, anticonvulsants, andneurotoxins. Electric stimulation of certain head or face nerves, suchas an occipital nerve, a great auricular nerve, a supra-clavicularnerve, and a cervical nerve, has been used to treat a variety ofheadache types, including migraines. Another approach to preventingheadaches is educating patients to recognize and avoid headache triggerswhich can include weather changes, bright light, strong odors, andstress. Again, these methods are typically only partially effective, andat best reduce the frequency of headaches.

Abortive treatments for cluster headaches include, e.g., inhalation of100% oxygen, occipital nerve block, 5ht1 antagonists, and ergotamines.Preventative therapy is an important approach for treating clusterheadaches, and drugs used in such treatments include beta-blockers,tricyclic antidepressants, anticonvulsants, cyproheptadine, and nsaids.But these approaches are also of limited effectiveness.

Approaches for treating tension headache include, e.g., symptomaticand/or abortive treatment involving administration of drugs such asaspirin, acetaminophen, and nsaids. Occasionally, tricyclic andantidepressants are used to treat severe and/or chronic tensionheadache. Approaches for treating head pain associated with trigeminalneuralgia include analgesic agents, which have an approximate 50%success rate and analgesic drugs, such as opioids or nsaids.

Given the prevalence of headache pain and given that, today, there doesnot appear to be a class of drugs or a treatment regimen reliablyeffective for relieving headache pain, there is a need for novel andeffective therapies preventing or alleviating headache pain.

Neuromuscular Anatomy of the Head

FIGS. 1 and 3 illustrate certain muscles in a human head. FIGS. 2 and 3illustrate the 12 pairs cranial nerves, which originate from the brainand innervate their respective target tissues and certain branch nervesthereof. The views shown in FIGS. 1-3 and the descriptions of FIGS. 1-3herein are not intended to be strictly anatomically accurate orcomplete, but rather illustrative, in a non-limiting manner, of certainfeatures of the present disclosure. For example, certain embodimentsprovide methods for reducing headache severity in a patient comprisingadministering pain reducing energy to a secondary or higher orderpostganglionic nerve branch that provides innervation for an area of thepatient's head, the area comprising, but not limited to, nerves andmuscles illustrated in FIGS. 1-3. Certain embodiments provide methodsfor reducing headache severity in a patient comprising administeringpain reducing energy to a secondary or higher order postganglionic nervebranch that provides innervation for an area of the patient's head andadministering a neurotoxin to an area of the patient's head, the areacomprising, but not limited to, nerves and muscles illustrated in FIGS.1-2. As used herein, “a secondary or higher-order branch of a neuron”refers to the following: if one follows a nerve from its cell body,along its axon to its dendrites, from proximal to distal, a first branchpoint of the axon is called a “primary branch point,” a second branchpoint of the axon is called a “secondary branch point,” a “higher-order”branch means a higher numbered branch point relative to some lowernumbered branch point referred to in a context. For example, in thecontext of “secondary or higher order,” higher order would refer to atertiary or higher numbered thing, and in the context of “primary orhigher order, higher order would refer to a secondary or higher numberedthing.

Referring to FIGS. 1-2, the olfactory nerve transmits certain odorinformation to the brain. The optic nerve transmits certain visualinformation to the brain. The oculomotor nerve innervates, e.g., thelevator palpebrae superioris, superior rectus, medial rectus, inferiorpractice, and inferior oblique muscles, which collectively perform mosteye movements. The trochlear nerve innervates, e.g., the superioroblique muscle, which is involved in depressing, pulling laterally, andintoning the eyeball.

The trigeminal nerve receives certain sensory information from the faceand innervates certain facial and mastication muscles. The abducensnerve provides innervation for, e.g., the lateral rectus muscle, whichis involved in abducting the eye. The facial nerve is involved inproviding motor innervation for certain muscles of the face involved infacial expression. The facial nerve also receives certain tasteinformation from the anterior ⅔ of the tongue and is involved inproviding secretomotor innervation to certain salivary glands and thelacrimal gland.

The vestibulocochlear nerve is involved in balance, movement, andsensing sound, rotation, and gravity. The glossopharyngeal nervereceives certain taste information from the posterior ⅓ of the tongue,and is involved in providing secretomotor innervation to the parotidgland and motor innervation to the stylopharyngeus. The vagus nerve isinvolved in providing motor innervation to certain laryngeal andpharyngeal muscles, and the vagus nerve also provides certainparasympathetic fibers to thoracic and abdominal viscera, down to thesplenic flecture. The vagus nerve further receives certain tasteinformation from the epiglottis. The accessory nerve is involved inproviding control of muscles of the neck and provides some overlappingfunctions of the vagus nerve. The hypoglossal nerve is involved inswallowing and speech articulation, and is involved in providing motorinnervation for certain glossal muscles.

The frontalis muscle originates at the superior curved line of occipitand the mastoid portion of the temporal bone, and inserts at the eyebrowand root of nose. The froutalis muscle is involved in moving the scalpand raising the eyebrows. The temporal muscle originates at the temporalfossa and fascia and inserts at the coronoid process of the lower jaw.The temporal muscle is involved in raising the lower jaw. The massetermuscle originates at the upper portion of the superior maxillary boneand inserts at the lower portion of the inferior maxillary bone. Themasseter muscle is involved in raising the lower jaw.

The risorius muscle originates at the fascia over the parotid gland andinserts at the angle of the mouth. The risorius muscle is involved indrawing back the corners of the month. The splenitis capitus muscleoriginates at the lower half of the ligamennun nuchae, the spinousprocess of the seventh cervical vertebra, and at the spinous processesof the upper three or four thoracic vertebrae, and the splenius capitusinserts at the sternocleidomastoideus, at the mastoid process of thetemporal bone, and at the surface on the occipital bone just below thelateral third of the superior nuchal line. The splenius capitis muscleis involved in head extension and head rotation.

The stylohyoid muscle originates at the styloid process and inserts atthe hyoid bone. The stylohyoid muscle is involved in depressing the jawand raising the hyoid bone. The suboccipital muscle refers to muscleslocated below the occipital bone, including the rectus capitis posteriormajor, rectus capitis posterior minor, obliquus capitis inferior, andobliquus capitis superior. The rectus capitis posterior major originatesat the spinous process of the epistropheous and inserts below thesuperior ridge of the occipit. The rectus capitis posterior major isinvolved in rotating the atlas and cranium. The rectus capitis posteriorminor originates at the posterior arch of the atlas and inserts belowthe inferior ridge of the occipit. The rectus capitis posterior minor isinvolved in drawing back the head. The obliquus capitis inferiororiginates at the spinous process of atlas and inserts at the transverseprocess of atlas. The obliquus capitis inferior is involved in rotatingatlas on axis. The obliquus capitis superior originates at thetransverse process of atlas and inserts between regions of occipit. Theobliquus capitis superior is involved in drawing back the head. Thedigastric muscle originates at the mastoid and lower jaw and inserts atthe hyoid bone. The digastric muscle is involved in depressing the jawin raising the hyoid bone. The buccinator muscle arises at alveolarborders of the superior and inferior maxillary bone and inserts at theorbicularis oris at the angle of the mouth. The buccinator muscle isinvolved in keeping food between grinders and in whistling.

The sternocleidomastoid muscle passes obliquely across the neck. Itoriginates at the medial third of the clavicle and inserts at themastoid process. The sternocleidomastoid muscle is involved in bendingthe head forward and to one side. The levator scapulae muscle arises attendinous slips from the transverse processes of the atlas and axis andfrom the posterior tubercles of the transverse processes of the thirdand fourth cervical vertebrae and it inserts at the vertebral border ofthe scapula, between the medial angle and the triangular smooth surfaceat the root of the spine. The levator scapulae muscle is involved inshrugging and in raising the medial angle of the scapula.

The scalenus medius muscle originates at the posterior tubercles oftransverse processes of the lower six cervical vertebrae and insert atthe upper surface of the first rib. The scalenus medius muscle isinvolved in the elevating the first rib and rotating the neck. Thescalenus anterior muscle originates at the anterior tubercles oftransverse processes of the third to six cervical vertebra and insertsat tubercle on inner border of the first rib. The scalenus anterior isinvolved in flexing the head sideways and forward.

The trapezius muscle arises at the external occipital protuberance andthe medial third of the superior nuchal line of the occipital bone (bothin the back of the head), at the ligamentum nuchae, at the spinousprocess of the seventh cervical (both in the back of the neck), and atthe spinous processes of all the thoracic vertebrae, and at thecorresponding portion of the supraspinal ligament (both in the upperback). The trapezius muscle inserts at the posterior border of thelateral third of the clavicle, at a tubercle at the apex of this smoothtriangular surface, and at the medial margin of the acromion, and intothe superior lip of the posterior border of the spine of the scapula.The trapezius muscle is involved in scapular elevation, retraction, anddepression.

The omohyoid muscle originates at the upper border of the scapula andinserts at the hyoid bone. The omohyoid muscle is involved in depressingand retracting the hyoid bone. The corrugator supercilii originates atthe medial end of the superciliary arch and inserts at deep surfaces ofthe skin, above the middle of the orbital arch. The corrugator isinvolved in drawing downward and medialward the eyebrow, producing thevertical wrinkles of the forehead. It is known as the “frowning” muscle.

The orbicularis oculi is a sphincter muscle of the eyelids. Itoriginates at, e.g., the nasal part of the frontal bone, at the frontalprocess of the maxilla in front of the lacrimal groove, and at themedial palpebral ligament. The palpebral portion of the muscle insertsat the lateral palpebral raphe. The orbital portion comprises lowerfibers that form on ellipse at the lateral palpebral commissure, and theupper fibers of this portion blend with the frontalis and corrugatormuscles. The lacrimal part (tensor tarsi) inserts at the superior andinferior tarsi medial to the puncta lacrimalia. The orbicularis oculi isinvolved in closing the eye. When the entire muscle is brought intoaction, the skin of the forehead, temple, and cheek is drawn toward themedial angle of the orbit, and the eyelids are firmly closed. The skinthen forms folds, especially radiating from the lateral angle of theeyelids; these folds become permanent in old age, and form the so-called“crows feet.”

The procerus muscle originates as tendinous fibers at the fasciacovering the lower part of the nasal bone and upper port of the lateralnasal cartilage and inserts at the skin over the lower part of theforehead between the two eyebrows, its fibers decussating with those ofthe frontalis. The procerus muscle is involved in pulling apart skinbetween the eyebrows, which assists in flaring the nostrils.

The nasalis muscle includes transverse and alar parts. The transversepart originates at the maxilla, above and lateral to the incisive fossa,and its fibers proceed upward and medially, expanding into a thinaponeurosis which is continuous on the bridge of the nose with that ofthe muscle of the opposite side, and with the aponeurosis of theprocerus. The alar part is attached at one end to the greater alarcartilage, and at the other to the integument at the point of the nose.

The levator labii superioris (or quadratus labii superioris) originatesat the side of the nose and inserts at the greater alar cartilage andskin of the nose and at the lateral part of the upper lip, blending withthe infraorbital head and with the orbicularis oris. The zygomaticmuscle arises at the malar bone and inserts at the orbicularis oris atthe angle of the mouth. The zygomaticus muscle is involved in drawingupwards and backwards the corners of the mouth. The levator anguli orismuscle originates at the canine fossa, immediately below theinfraorbital foramen and inserts at the angle of the mouth,intermingling with the zygomaticus, triangularis, and orbicularis oris.

The orbicularis oris comprises numerous strata of muscle fiberssurrounding the orifice of the mouth, the muscle fibers are derivedpartly from other facial muscles which insert into the lips and partlyfrom fibers proper to the lips. In addition, certain fibers connect theorbicularis oris muscle with the maxilae and the septum of the nose andwith the mandible.

The platysma is a superficial muscle that overlaps thesternocleidomastoid. It originates at the fascia covering the upperparts of the pectoralis major and deltoideus; and inserts at the bonebelow the oblique line, at the skin and subcutaneous tissue of the lowerpart of the face, many of these fibers blending with the muscles aboutthe angle and lower part of the mouth. Sometimes platysma muscle fiberscan be traced to the zygomaticus or to the margin of the orbicularisoculi.

The depressor labii inferioris (or quadratus labii inferioris) is afacial muscle involved in lowering the bottom lip. It originates at theoblique line of the mandible and inserts at the skin of the lower lip,blending in with the orbicularis oris muscle. At its origin, thedepressor labii is continuous with the fibers of the platysma muscle.The depressor labii inferioris is involved in depressing the lower lip.The depressor anguli oris originates at the oblique line of the mandibleand inserts, by a narrow fasciculus, at the angle of the mouth. Thedepressor anguli oris is involved in frowning.

The sternohyoid muscle is a thin, narrow muscle attaching the hyoid boneto the sternum, one of the paired strap muscles of the infrahyoidmuscles, and it is involved in depressing the hyoid bone. Thesternohyoid muscle originates at the posterior border of the medial endof the clavicle, at the posterior sternoclavicular ligament, and at theupper and posterior part of the manubrium sterni and inserts, by shorttendinous fibers, at the lower border of the body of the hyoid bone.

The lesser occipital nerve or small occipital nerve is a spinal nervearising between the first and second cervical vertebrae, along with thegreater occipital nerve. It innervates the scalp in the lateral area ofthe head behind the ear, and arises from the lateral branch of theventral raimis of the second cervical nerve, sometimes also from thethird; it curves around and ascends along the posterior border of thesternocleidomastoideus. Near the cranium it perforates the deep fascia.It continues upward along the side of the head behind the auricula,supplying the skin and communicating with the greater occipital, thegreat auricular, and the posterior auricular branch of the facial nerve.The smaller occipital varies in size, and is sometimes duplicated. Itgives off an auricular branch, which supplies the skin of the upper andback part of the auricula, communicating with the mastoid branch of thegreat auricular. This branch is occasionally derived from the greateroccipital nerve.

The greater occipital nerve is a spinal nerve arising from the dorsalprimary rami of cervical spinal nerve two, between the first and secondcervical vertebrae, along with the lesser occipital nerve. It isinvolved in innervating the scalp at the top of the head, over the ear,and over the parotid glands. The zygomatic-temporal nerve arises in thepterygopalatine fossa. It enters the orbit by the inferior orbitalfissure, and divides into two branches, the zygomaticotemporal nerve andzygomaticofacial nerve. The zygomatic nerve carries sensory fibers fromthe skin. It also carries post-synaptic parasympathetic fibers(originating in the pterygopalatine ganglion) to the lacrimal nerve viaa communication. These parasympathetic fibers come from the facialcranial nerve, and are involved in providing innervation for thelacrimal gland.

The trigeminal nerve is involved in providing sensation in the face.Sensory information from the face and body is processed by parallelpathways in the central nervous system. The fifth nerve is primarily asensory nerve, but it also has certain motor functions. The trigeminalnerve is the largest of the cranial nerves, and its name derives fromthe fact that it has three major branches: the ophthalmic nerve(V.sub.1), the maxillary nerve (V.sub.2), and the mandibular nerve(V.sub.3). The mandibular nerve has both sensory and motor functions.The three branches converge on the trigeminal ganglion (also called thesemilunar ganglion or gasserian ganglion), which contains the cellbodies of incoming sensory nerve fibers. The trigeminal ganglion is, incertain aspects, analogous to the dorsal root ganglia of the spinalcord, which contain the cell bodies of incoming sensory fibers from therest of the body. From the trigeminal ganglion, a large sensory rootenters the brainstem at the level of the pons. Immediately adjacent tothe sensory root, a smaller motor root emerges from the pons at the samelevel. Motor fibers pass through the trigeminal ganglion on their way toperipheral muscles, their cell bodies located in the motor nucleus ofthe fifth nerve, deep within the pons. Motor fibers are also distributed(together with sensory fibers) in branches of the mandibular nerve.

The areas of cutaneous distribution (dermatomes) of the three branchesof the trigeminal nerve generally have sharp borders with relativelylittle overlap (unlike dermatomes in the rest of the body, which showconsiderable overlap). Injection of local anesthetics such as lidocaineresults in the loss of sensation from well-defined areas of the face andmouth. For example, the teeth on one side of the jaw can be numbed byinjecting the mandibular nerve.

The ophthahnic, maxillary and mandibular branches leave the skullthrough three separate foramina: the superior orbital fissure, theforamen rotundum and the foramen ovale. The ophthalmic nerve carriescertain sensory inforuration from the scalp and forehead, the uppereyelid, the conjunctiva and cornea of the eye, the nose (including thetip of the nose), the nasal mucosa, the frontal sinuses, and parts ofthe meninges (the dura and blood vessels). The maxillary nerve carriescertain sensory inforuration from, e.g., the lower eyelid, cheek, nose,upper lip, upper teeth, upper gums, nasal mucosa, palate of the pharynx,roof of the pharynx, sphenoid sinus, and parts of the meninges. Themandibular nerve carries certain sensory information from, e.g., thelower lip, the lower teeth, the lower gums, the chin, the jaw (exceptthe angle of the jaw), parts of the external ear, and parts of themeninges. The mandibular nerve carries certain touch/position andcertain pain/temperature sensation from the mouth, and some of itsbranches, e.g., the lingual nerve, carries multiple types of nervefibers that do not originate in the mandibular nerve.

The glossopharyngeal nerve is the ninth pair of twelve pairs of cranialnerves. It exits the brainstem out from the sides of the upper medulla,just rostral (closer to the nose) to the vagus nerve. Theglossopharyngeal nerve receives certain sensory fibers from theposterior ⅓ of the tongue, the tonsils, the pharynx, the middle ear, andthe carotid sinus. It supplies some parasympathetic fibers to theparotid gland via the otic ganglion, and it supplies some motor fibersto stylopharyngeus muscle. It also contributes to the pharyngeal plexus.From the medulla oblongata, the glossopharyngeal nerve passes laterallyacross the flocculus, and leaves the skull through the central part ofthe jugular foramen, in a separate sheath of the dura mater, lateral toand in front of the vagus and accessory nerves. Within the jugularforamen, the glossopharyngeal nerve forms the superior ganglion, and theglossopharyngeal nerve is also associated with an inferior ganglion.

In its passage through the jugular foramen, it grooves the lower borderof the petrous part of the temporal bone; and, at its exit from theskull, passes forward between the internal jugular vein and internalcarotid artery. It descends in front of the latter vessel, and beneaththe styloid process and the muscles connected with it, to the lowerborder of the stylopharyngeus. It then curves forward, forming an archon the side of the neck and lying upon the stylopharyngeus and middlepharyngeal constrictor muscle. From there it passes under cover of thehypoglossal muscle, and is distributes to the palatine tonsil, themucous membrane of the fauces and base of the tongue, and the mucousglands of the mouth.

Branches of the glossopharyngeal nerve include tympanic,stylopharyngeal, sonsillar, nerve to carotid sinus, branches to theposterior third of tongue, lingual branches, and vagus nerve branches.

Energy Generating Units

In certain embodiments, an energy delivery device can comprise at leastone energy generating unit configured to provide electrical energy. Incertain embodiments, an energy delivery device can comprise a backupenergy generating unit configured to provide electrical energy in case aprimary energy delivery device fails. In certain embodiments, an energygenerating unit can be configured to provide electromagnetic energy of avariety of wavelengths, including gamma rays, x-rays, ultraviolet, blue,red, visible, infrared, radio, microwave wavelengths, and combinationsthereof. In certain embodiments, an energy generating unit can beconfigured to provide ultrasonic energy. In certain embodiments, anelectrical generating unit can be configured to provide electricalenergy. In certain embodiments, an electrical generating unit can beconfigured to provide heat energy. In certain embodiments, an electricalgenerating unit can be configured to provide cryogenic energy. Incertain embodiments, an electrical generating unit can be configured toprovide other types of energy known to those of skill in the art.

In certain embodiments, energy generating units provide laser energy.Exemplary laser generating units include argon lasers, KTP lasers,Nd:YAG lasers, excimer lasers, alexandrite lasers, hohnium:YAG lasers,Er:YAG, Er:YSGG, infrared gas lasers, ArF excimer lasers. XeCl excimerlasers, nitrogen lasers, and Nd:YLF lasers.

Electrode Probes

In certain embodiments, the energy delivery device can comprise anelectrode probe, coupled to an energy generating unit, the electrodeprobe carrying one or multiple electrodes configured to deliver energyprovided by the energy generating unit in amounts and temporal patternseffective to stimulate an activity of a motor nerve, a sensory nerve, amuscle, or a combination thereof or effective to inhibit, permanently ortemporarily, an activity of a motor nerve, a sensor nerve, a muscle, ora combination thereof. In certain embodiments, an energy delivery devicecan comprise an electrode probe coupled to an energy generating unit,the electrode probe carrying one or multiple electrodes configured todeliver energy provided by the energy generating unit in amounts andtemporal patterns effective to ablate a motor nerve and/or a sensorynerve.

In certain embodiments, an electrode probe can comprise one or more of avariety of cross-sectional shapes and forms, such as circular,rectangular, elliptical cross, conical, pyramidal, solid, and hollow.Surfaces of an electrode probe can comprise one or more of a variety ofshapes and forms, such as smooth, textured, flat, concave, and convex. Alongitudinal shape of an electrode probe can comprise one or more of avariety of forms, such as straight, arced, bent, or a combinationthereof. In certain embodiments, an electrode probe can comprise aneedle shape that allows for efficient percutaneous penetration intomuscle and other tissues.

In certain embodiments, an electrode probe can comprise apenetration-depth measuring and/or limiting device, such as anadjustable or non-adjustable collar positioned at a desired distancefrom an end portion of an electrode probe configured for percutaneousinsertion into muscle of a patient.

In certain embodiments, an electrode probe comprises a single tip forsingle-point, percutaneous penetration of muscle and other tissue. Incertain embodiments, an electrode probe comprises a single tipconfigured for positioning at a skin surface. In certain embodiments, anelectrode probe comprises multiple tips; some or all of which can beconfigured for percutaneous penetration and some or all of which can beconfigured for superficial positioning at a skin surface.

In certain embodiments, an electrode probe, an auxiliary probe, or both,of an energy delivery device, can comprise one or a plurality ofsensors. Exemplary sensors include temperature sensors, energyconduction sensors, energy impedance sensors, voltage sensors, wattagesensors, amperage sensors, and optical sensors. In certain embodiments,information gathered by such sensors is indicative of an identity oftissues (e.g., adipose, bone, nerve, and muscle tissue) in a proximityof the sensor. In certain embodiments, information gathered by sensorsis indicative a tissue condition (e.g., healthful, diseased, active,inactive, stimulated, and ablated) in a proximity of the sensor.

In certain embodiments, an electrode probe, an auxiliary probe, or bothcan comprise insulating elements effective to reduce or block energydelivery from an electrode to a non-target tissue in a proximity of atarget motor neuron branch, and thereby focus energy delivery to aspecific region of tissue. In certain embodiments, an electrode probeand/or an auxiliary probe comprising an insulating element, can achieveasymmetric energy delivery. In certain embodiments, an electrode probeand/or an auxiliary probe comprising an insulating element can achievesymmetric energy delivery. Insulating elements can be made from avariety of materials, such as Teflon®, PTFE, a polyimide material, apolyamide material, or other insulative material. The insulatingmaterial may be coated, bonded, glued, welded, etc. onto an electrode orother component of an electrode probe or onto an auxiliary probe.

In certain embodiments, an electrode probe comprises a metal, such asstainless steel, nickel, titanium, platinum, aluminum, iron, and alloysthereof. In certain embodiments, an electrode probe comprises anelectromagnetic energy transmission element. In certain embodiments, anelectromagnetic energy transmission element can be configured totransmit electromagnetic radiation in wavelengths and amounts effectiveto illuminate, to stimulate, and/or to photoablate a tissue in aproximity of the electrode, and such transmitted electromagneticradiation can comprise, e.g., at least one wavelength selected fromultraviolet, blue, red, visible, infrared, radio, and microwave.

In certain embodiments, an electrode probe comprises energy transmissionelements configured to transmit heat energy, cryogenic energy, or acombination thereof. Such heat and cryogenic energy transmissionelements can be configured to transmit heat or cryogenic, energy,respectively, in amounts effective to stimulate and/or ablate a tissuein a proximity of an electrode. In certain embodiments, an electrodeprobe comprises an ultrasonic energy transmission element, andultrasonic energy transmission elements can be configured to transmitultrasonic energy in amounts effective to stimulate and/or to ablate atissue in a proximity of the electrode.

In certain embodiments, an electrode probe comprises at least one of anelectromagnetic transmission element, a heat energy transmissionelement, cryogenic energy transmission element, and an ultrasonic energytransmission element. In certain embodiments, electrodes comprise atleast one metal, such as stainless steel, nickel, titanium, platinum,aluminum, iron, and alloys thereof. In certain embodiments, electrodescomprising multiple metals and/or alloys can be joined by, e.g.,crimping, swaging, soldering, welding, and/or adhesive bonding.

In certain embodiments, the electrode probe can include features fromthe device disclosed in U.S. patent application Ser. No. 10/870,202,filed on Jun. 17, 2004, and incorporated by reference herein in itsentirety.

Control Units

In certain embodiments, an energy delivery device can comprise, or becoupled to, one or more control units. A control unit can configure anamount of energy and a temporal pattern of energy provided by an energygenerating unit to one or a plurality of electrode probes and/or energytransmission members, either automatically (e.g. by running amicroprocessor program), under the control of an operator, (e.g., by oneor more manual input interfaces), or by a combination of automatic andmanual inputs.

Stimulation Energy

In certain embodiments, an amount of energy provided by an energygenerating unit can be controlled to be stimulatory toward, forinstance, a nerve, a branch of a nerve, a muscle, or combinationsthereof; and such stimulatory energy can be effective to result in adepolarization of a nerve, a muscle, or both. In certain embodiments, astimulation energy delivered by an energy transmission member to amuscle, a nerve, or both, can be effective to result in a musclecontraction.

In certain embodiments, a stimulatory amount of electromagnetic energycan be provided by an energy generating unit in the form of laser energyin a range from about 0.1 mJ to about 5 mJ with a spot size of about 5.mu.m to about 600 .mu.m. In certain embodiments, a stimulatory amountof electromagnetic energy can be provided in the form of laser energy ofabout 1 mJ, about 2 mJ, about 3 mJ, about 4 mJ, and about 5 mJ. Incertain embodiments, a stimulatory amount of electromagnetic energy canbe provided in a laser comprising a beam width of about 5 .mu.m, about10 .mu.m, about 20 .mu.m, about 30 .mu.m, about 40 .mu.m, 50 .mu.m,about 100 .mu.m, about 200 .mu.m, about 300 .mu.m, about 400 .mu.m,about 500 .mu.m, and about 600 .mu.m. In certain embodiments, astimulatory amount of laser energy can be delivered in micropulseshaving a duration of about 1 ps, about 2 ps, about 3 ps, about 4 ps,about 5 ps, about 6 ps, about 7 ps, about 8 ps, about 1 ps, about 10 ps,about 15 ps, about 20 ps, about 30 ps, about 50 ps, and about 100 ps. Anenvelope of such micropulses can form a macropulse of about 1 .mu.s,about 2 .mu.s, about 5 .mu.s, about 10 .mu.s, about 20 .mu.s, about 30.mu.s, about 40 .mu.s, about 50 .mu.s, about 75 .mu.s, and about 100.mu.s. In certain embodiments, a macropulse of stimulatory laser energycan be delivered at a rate of about 1 Hz, about 5 Hz, about 10 Hz, about20 Hz, about 30 Hz, about 40 Hz, about 50 Hz, about 75 Hz, and about 100Hz.

Electromagnetic energy absorption characteristics of many biologicaltissues, such as nerve tissue and muscle tissue, often closelycorresponds to the electromagnetic energy absorption characteristics ofwater. In certain embodiments, photoablation of biological tissues canbe minimized or avoided in the process of delivering a stimulatoryamount of electromagnetic energy by providing electromagnetic energy inwavelengths poorly absorbed by water, such as wavelengths of about 1.mu.m, about 1.25 .mu.m, about 1.5 .mu.m, about 1.75 .mu.m, about 2.mu.m, about 2.25 .mu.m, about 2.5 .mu.m, about 2.75 .mu.m, about 2.75.mu.m, about 4 .mu.m, about 4.25 .mu.m, about 4.5 .mu.m, about 4.75.mu.m, about 5 .mu.m, about 5.25 .mu.m, and about 5.5 .mu.m.

In certain embodiments, a free electron laser (FEL), tunable in toprovide infrared spectrum electromagnetic wavelengths from about 2 .mu.mto about 10 .mu.m, can provide stimulatory electromagnetic energy. Incertain embodiments, a FEL can provide stimulatory electromagneticenergy in micropulses, each about 1 ps in duration, with a repetitionrate of about 3 GHz. The envelope of such micropulses can form amacropulse of about 1 .mu.s to about 10 .mu.s, which can be delivered ata rate of up to about 30 Hz.

In certain embodiments, an energy generating unit can be configured toprovide a stimulatory amount of electrical energy in the form ofelectrical energy, such as low frequency DC energy pulses of e.g., about0.1 Hz, about 0.5 Hz, about 1 Hz, about 2 Hz, about 3 Hz, about 4 Hz,about 5 Hz, about 6 Hz, about 7 Hz, about 8 Hz, about 9 Hz, and about 10Hz, at low amps of for instance, about 0.1 mA, about 0.25 mA, about 0.5mA, about 0.75 mA, about 1 mA, about 2 mA, about 3 mA, about 4 mA, about5 mA, about 10 mA, about 15 mA, about 20 mA, and about 25 mA, withoutgenerating an ohmic heating effect. Such neurostimulatory electricalenergy can be applied as DC square pulses having a pulse width of about1 ms, about 10 ms, about 25 ms, about 50 ms, about 75 ms, about 100 ms,about 125 ms, about 150 ms, about 175 ms, and about 200 ms.

In certain embodiments, an energy generating unit can provide astimulatory amount of electrical energy in the form of electrical energycomprising an amplitude of about 1 mA, about 2 mA, about 3 mA, about 4mA, about 5 mA, about 6 mA, about 7 mA, about 8 mA, about 9 mA, about 10mA; a pulse width of about 0.1 ms, about 0.2 ms, about 0.3 ms, about 0.4ms, about 0.5 ms, about 0.6 ms, about 0.7 ms, about 0.8 ms, about 0.9ms, and about 1 ms; and a frequency of about 1 Hz, about 2 Hz, about 3Hz, about 4 Hz, and about 5 Hz.

In certain embodiments, an activity of a biological tissue, e.g., muscleor nerve tissue, resulting from the delivery, to a second orhigher-order postganglionic nerve branch or other nerve of a patient'shead, can be observed visually as, e.g., a muscle twitch or electricallyby an electrode configured to detect a depolarization of the nerve.

Ablation Energy

In certain embodiments, an amount of energy provided by an energygenerating unit can be controlled to result in an ablation of a nerve, abranch of a nerve, or both. In certain embodiments, an ablative amountof electromagnetic energy can be provided in the form of laser energy ina range from about 2.5 mJ to about 250 mJ with a spot size of about 5.mu.m to about 1000 .mu.m. In certain embodiments, an ablative amount oflaser energy can be provided in the form of pulsed laser energy of about1 mJ, about 3 mJ, about 5 mJ, about 10 mJ, about 20 mJ, about 30 mJ,about 40 mJ, about 50 mJ, about 75 mJ, about 100 mJ, about 158 mJ, about200 mJ, and about 250 mJ and can comprise a spot size of about 5 .mu.m,about 10 .mu.m, about 20 .mu.m, about 30 .mu.m, about 40 .mu.m, 50.mu.m, about 100 .mu.m, about 200 .mu.m, about 300 .mu.m, about 400.mu.m, about 500 .mu.m, about 600 .mu.m, about 700 .mu.m, about 800.mu.m, about 900 .mu.m, and about 1000 .mu.m.

In certain embodiments, an ablative amount of laser energy can bedelivered in micropulses having a duration of about 10 ps, about 20 ps,about 50 ps, about 100 ps, about 250 ps, about 500 ps, about 1 ns, about10 ns, about 25 ns about 50 ns, about 75 ns, and about 100 ns. Anenvelope of such micropulses can form a macropulse of about 1 .mu.s,about 10 .mu.s, about 25 .mu.s, about 50 .mu.s, about 100 .mu.s, about250 .mu.s, about 500 .mu.s, about 750 .mu.s, about 1 ms, about 10 ms,about 50 ms, and about 100 ms. In certain embodiments, a macropulse ofstimulatory electromagnetic energy can be delivered at a rate of about 1Hz, about 5 Hz, about 10 Hz, about 20 Hz, about 30 Hz, about 40 Hz,about 50 Hz, about 75 Hz, and about 100 Hz.

In certain embodiments, the stimulatory amount of electromagneticenergy, the ablative amount of electromagnetic energy or both, can beprovided by, e.g., a YAG laser, tunable to provide electromagneticwavelengths in the LTV, visible, and infrared portion of the spectrum ora lead-salt laser, tunable to provide wavelength of about 4 .mu.m.

In certain embodiments, a control unit can be coupled to an energygenerating unit, a laser transmission element, and a sensor that,together, facilitate automatic adjustment of laser delivery parameters,e.g., pulse duration, repetition rate, spot size, and total amount oflaser energy based on a sensed condition of the tissue to which thelaser energy is delivered so as to achieve a desired condition, e.g.temperature, of the target tissue. In some embodiments, automaticshutoff of the laser occurs upon reaching the desired condition thelaser energy delivery. This enables control and optimization of thedesired effect (e.g., stimulation and/or ablation) of laser energydelivery on the target tissues.

In certain embodiments, an ablative amount of electromagnetic energy canbe provided in the form of radiofrequency (RF) energy of, for instance,about 100 kHz, about 250 kHz, about 500 kHz, about 750 kHz, about 1 mHz,about 2.5 mHz, about 5 mHz, about 7.5 mHz, and about 10 mHz applied at,for instance, about 0.1 A, about 0.25 A, about 0.5 A, about 1 A, about 2A, about 5 A, and about 10 A.

In certain embodiments, the delivery of an ablative amount of RF energy,heat energy, laser energy, electric energy, or combinations thereof canresult in a temperature of a target nerve of about 40.degree. C., about45.degree. C., about 50.degree. C., about 55.degree. C., about60.degree. C., about 70.degree. C., about 80.degree. C., about90.degree. C., and about 100.degree. C. In certain embodiments, deliveryof an ablative amount of cryogenic energy can result in a temperature ofa target nerve, nerve branch, or both, of about −80.degree. C., about−70.degree. C., about −60.degree. C., about −50.degree. C., about−40.degree. C., about −30.degree. C., about −20.degree. C., about−10.degree. C., and about 0.degree. C.

In certain embodiments, a control unit can configure an RF transmissionelement of an electrode probe to operate as a RF energy transmitter oras a RF energy receiver. A control unit can provide for monopolaroperation of an electrode probe by configuring multiple RF transmissionelements of an electrode probe to transmit RF energy to a common RFenergy receiver. In certain embodiments, a control unit can provide forbipolar operation of an electrode probe by configuring pairs of RFenergy transmission elements of an electrode probe such that oneelectrode of the pair operates as a RF energy transmitter and the otheroperates as a RE energy receiver. In certain embodiments, a control unitcan switch, randomly or in an ordered sequence, the transmitter andreceiver operations of RE energy transmission elements within a pair aswell the identity of electrode probes operative as a pair. In certainembodiments, electrodes probes configured to deliver RE energy can alsobe configured to deliver neurostimulatory electrical energy, asdescribed herein.

In certain embodiments, the control of energy delivery afforded by acontrol unit allows temporary nerve-conduction interruption that ispermanent or temporary, which can last for a period of several months oryears. This flexibility allows for patients and physicians to evaluatetemporary treatment before choosing longer or permanent treatmentoptions.

Neurotoxins

In certain embodiments, neurotoxins capable of producing reversiblemuscle paralysis without a concomitant degeneration of muscle or nervoustissue can be administered, in a therapeutically effective amount thatreduces a headache pain in a patient, to a neuron in combination withthe delivery of neurostimulatory and neuroablative energy as describedherein. In certain embodiments, a neurotoxin is a Botulinum toxin, suchas Botulinum toxin A and tetanus toxin.

In certain embodiments, a neurotoxin can be administered to reduce ahead pain associated with muscle spasm, ithiscile contraction, vasculardisturbances, neuralgia, and neuropathy. In certain embodiments, aneurotoxin can be administered intramuscularly to reduce headache pain,and an amount of administered neurotoxin effective to reduce headachepain does not result in paralysis of a muscle. In certain embodiments,an amount of administered neurotoxin effective to reduce headache paindoes result in a paralysis of a muscle.

As used herein, the term “Neurotoxin” includes invertebrate proteintoxins and biologically active peptide fragments thereof. In certainembodiments, a neurotoxin comprises Botulinum toxin. Serotype A of thistoxin is commercially available under the tradename BOTOX®. In certainembodiments, a neurotoxin comprises a pentavalent toxoid composition ofall eight known Botulinum serotypes. In certain embodiments, aneurotoxin comprises a subcombination of the eight known Botulinumserotypes. In certain embodiments, a neurotoxin can comprise a tetanustoxin and/or a biologically active peptide fragments thereof, such asthe Ibe fragment of tetanus toxin. In certain embodiments, a neurotoxincan comprise a form that is nontetragenic and does not induce adetectable immune response to the toxin antigen. In certain embodiments,a neurotoxin can be administered in a pharmaceutical compositioncomprising pharmaceutically acceptable salts, buffers, carriers,chelating agents, excipients, and combinations thereof.

A therapeutically effective dose of a neurotoxin to be administered canvary with the age, condition, and weight of the patient to be treated aswell as the site and method of administration of the neurotoxin, thestimulatory energy, and the ablative energy. The potency of theneurotoxin will also be considered. In certain embodiments, atherapeutically effective dose of a neurotoxin can be about 1 pg, about10 pg, about 25 pg, about 50 pg, about, 100 pg, about 250 pg, about 500pg, about 750 pg, about 1 ng, about 10 ng, about 25 ng, about 50 ng andabout 100 ng. In certain embodiments, a therapeutically effective doseof a neurotoxin can be about 1 microunit, about 5 microunits, about 10microunits, about 20 microunits, about 50 microunits, about 100microunits, about 250 microunits, about 500 microunits, about 750microunits, about 1 milliunit, about 5 milliunits, about 10 milliunits,about 20 milliunits, about 50 milliunits, about 100 milliunits, about250 milliunits, about 500 milliunits, about 750 milliunits, about 1unit, about 5 units, about 10 units, about 20 units, and about 50 units.As used herein, one unit of a neurotoxin is an amount of toxin thatkills 50% of a group of mice that were disease-free prior to inoculationwith the toxin.

In certain embodiments, a neurotoxin can be administered by injection.In certain embodiments, a low dosage of a neurotoxin may initially beadministered at a target region to determine the patient's sensitivityto, and tolerance of, the neurotoxin. Additional injections of the sameor different dosages can be administered as necessary. In certainembodiments, a neurotoxin can be administered by subcutaneous injection,perivascular injection, or intramuscular injection (e.g., to aneuromuscular endplate or neuromuscular junction of a secondary orhigher order postganglionic nerve branch, or other, ablated in a patientaccording to a method for treating headache disclosed herein).

In certain embodiments, the administration of a neurotoxin andneuroablative energy can occur simultaneously or sequentially in asingle procedure or in multiple procedures. In certain embodiments,injections of a neurotoxin can be repeated as necessary. For instance,Botulinum toxin A administered into or near muscle tissue typicallyproduces flaccid paralysis at target site muscles for up to about 3 toabout 6 months. Reduction of headache pain in patients who received theneurotoxins extramuscularly can also persist for extended periods oftime, such as up to about 3 to about 6 months.

In certain embodiments, intramuscular injection of a neurotoxin caninvolve an electromyographical (“EMG”) injection, in which theneurotoxin is administered percutaneously into a target site, such as amuscle comprising a neuromuscular junction. For instance, a monopolarhollow bore needle can be inserted through skim and its positionadjusted, based on observation of the EMG signal, such that theneurotoxin is delivered to the neuromuscular junction withoutsubstantial systemic distribution.

EXAMPLES

Twenty patients, each of whom suffered from migraine headaches, wereentered into a single arm efficacy study of selective percutaneousneurolysis treatment method. Prior to and after treatment, each patientanswered questionnaires. Pretreatment questionnaires established that 13of the 20 patients suffered migraine headaches more than 15 days permonth and that 7 of the 20 patients suffered from migraine headachesless than 15 days per month. Pretreatment questionnaires establishedthat 5 of the 20 patients suffered from migraine headaches lasting formore than 72 hours; 11 of the 20 patients suffered from migraineheadaches lasting for 4 to 72 hours, and 4 of the 11 patients sufferedfrom migraine headaches lasting for less than 4 hours. Pretreatmentquestionnaires established that 15 of the 20 patients suffered severedisability resulting from migraine headache and that 5 of the 20patients suffered from mild or no disability resulting from migraineheadache. Post treatment questionnaires established that following aselective percutaneous neurolysis treatment 10 of the 20 patientsexperienced a decrease in migraine headache frequency; 10 of the 20patients experienced no decrease in migraine headache frequency; 1 ofthe 20 patients experienced an increase in migraine headache eventfrequency; 14 of the 20 patients experienced reduced disabilityresulting from migraine headache; 4 of the 20 patients experienced nochange in disability resulting from migraine headache; 2 of the 20patients experienced increased disability resulting from migraineheadache. Overall, 18 of the 20 patients had a decrease in at least onemigraine headache symptom.

The present disclosure is capable of embodiments additional to thosedescribed herein, and the disclosure is not limited in its applicationto the embodiments described herein, or to the details of the particularembodiments described herein. The terminology used herein is for thepurpose of describing the headache treatment methods of the presentdisclosure, and the present disclosure, as described herein, hasnumerous equivalents within its scope.

I claim:
 1. A headache treatment method comprising: providing an energydelivery device comprising a single tip; locating a secondary orhigher-order branch of a postganglionic nerve that provides innervationfor a patient's head, wherein the locating comprises: identifying atarget region, of the patient's head, comprising the nerve branch;percutaneously advancing a portion of the energy delivery device througha single point to position the portion of the energy delivery devicewithin the target region; and applying, from the positioned portion ofthe energy delivery device to the target region, an amount of energyeffective to result in a stimulation activity of the nerve branch; afterobserving the stimulated nerve branch activity, delivering, from theenergy delivery device to the nerve branch, energy in an amounteffective to reduce a headache severity in the patient; and delivering,a neurotoxin to an area of the patient's head.
 2. The method of claim 1,where delivering the neurotoxin to the area of the patient's headcomprises delivering the neurotoxin to a nerve or a muscle.
 3. Themethod of claim 1, where the neurotoxin is delivered with aneurostimulatory energy.
 4. The method of claim 1, where the neurotoxinis delivered without resulting in paralysis of a muscle.
 5. The methodof claim 1, where the neurotoxin is delivered by an injected selectedfrom the group consisting of a subcutaneous injection, a perivascularinjection, and an intramuscular injection.
 6. The method of claim 1,where the neurotoxin is delivered using an electromyographical signal toadjust a position of the delivery.
 7. The method of claim 1, wherein theheadache severity comprises at least one of a degree of pain, afrequency, and a duration of the headache.
 8. The method of claim 1,wherein the delivered energy comprises at least one of ultrasoundenergy, heat energy, cryogenic energy, electromagnetic energy,ultraviolet light energy, a blue light energy, an infrared light energy,an x-ray energy, a gamma-ray energy, and a microwave energy.
 9. Themethod of claim 1, wherein the amount of delivered energy effective toreduce the headache pain is effective to ablate the neuron.
 10. Themethod of claim 1, further comprising at least one of detecting thestimulated nerve branch activity with electromyography, and detectingthe stimulated nerve branch activity as nerve conduction between twoelectrodes.
 11. The method of claim 1, further comprising: locating asensory nerve innervating the patient's head; and applying, from thepositioned portion of the energy delivery device to the sensory nerve,an amount of energy effective to reduce the headache severity in thepatient.
 12. The method of claim 11, wherein the sensory nerve comprisesat least one of a second occipital nerve, a third occipital nerve, azygomaticotemporal nerve, a trigeminal nerve, a glossopharyngeal nerve.13. The method of claim 1, wherein the nerve branch comprises a moneuron, a sympathetic neuron, or a tertiary or higher-order branch. 14.The method of claim 13, wherein the motor neuron innervates a muscleselected from the group consisting of a frontalis muscle, a corrugatorsuperculii muscle, an orbicularis oculi muscle, a procerus muscle, anasalis muscle, a levator labii superioris muscle, a zygomaticus majormuscle, a zygomaticus minor muscle, a levator anguii oris muscle, amodialus muscle, a platysma paris muscle, a platysma labialis muscle, adepressor labii inferioris muscle, a depressor anguli oris muscle, aplatysma pars modialaris muscle, a platysma pars labialis muscle, aplatysma pars mandibularis muscle, a temporalis muscle, an occipatalismuscle, a risorius muscle, a masseter muscle, a splenius capitus muscle,a stylohyoid muscle, a suboccipital muscle, a digastric muscle, abuccinator muscle, a sternocleidomastoid muscle, a levator scapulaemuscle, a scalenus medius muscle, a scalenus anterior muscle, atrapezius muscle, and an omohyoid muscle.
 15. The method of claim 13,wherein the nerve is selected from at least one of a facial nerve, anabducens nerve, an oculomotor nerve, a trochlear nerve, a trigeminalnerve, a glossopharangeal nerve, a hypoglossal nerve, and an accessorynerve.
 16. The method of claim 13, wherein the nerve branch comprises abranch of a facial nerve selected from a temporal branch, a zygomaticbranch, a buccal branch, a mandibular branch, and a cervical branch. 17.The method of claim 13, wherein the nerve branch is selected from atleast one of a superior division of the oculomotor nerve and an inferiordivision of the oculomotor nerve.
 18. The method of claim 13, whereinthe nerve branch comprises a mandibular branch of the trigeminal nerve,a mylohyoid branch of the mandibular branch, or a pharyngeal branch ofthe glossopharyngeal nerve.
 19. The method of claim 13, wherein thenerve branch comprises a branch of the hypoglossal nerve selected from ameningeal branch, a thyrohyoid branch, a descending branch, and amuscular branch.
 20. The method of claim 13, wherein the nerve branchcomprises an angular nerve.